Abstract:
Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer\'s patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.
摘要:
口服疫苗是注射疫苗的一种安全、方便的替代品,在预防重大传染病方面具有巨大潜力。然而,恶劣的胃肠(GI)环境,粘液屏障,低免疫原性,缺乏有效和安全的粘膜佐剂是口服疫苗的主要挑战。近年来,基于纳米颗粒的策略对于改善口服疫苗递送具有吸引力。这里,制备了树枝状纤维纳米二氧化硅(DFNS)接枝肉松多糖(CDP)纳米颗粒(CDP-DFNS),并研究了其对免疫应答的影响。CDP-DFNS促进小鼠骨髓来源的树突状细胞(BMDCs)的抗原摄取,并在体外诱导DCs的活化。此外,体内实验,结果表明,Peyer贴剂(PPs)对CDP-DFNS/BSA的吸收效率最好。然后CDP-DFNS/BSA显着激活固有层(LP)中的DCs,PPs和肠系膜淋巴结(MLN)中的T/B细胞。此外,疫苗接种后期的记忆T细胞反应强于其他组。此外,CDP-DFNS/BSA增强的BSA特异性抗体IgG,IgA生产,和SIgA分泌,在诱导强混合的Th1/Th2应答和粘膜抗体应答方面是有效的。这些结果表明CDP-DFNS作为口服疫苗佐剂递送系统值得进一步考虑。